Cancer is a major health concern worldwide, accounting for millions of deaths and untold pain and suffering each year. The biologic heterogeneity of this disease and the vast populations afflicted pose the pivotal questions of whom to treat and with which therapies, challenges that can only be addressed through the development of more accurate and informative biomarkers. Peripheral blood circulating tumor cells (CTCs) recently have been detected and shown to have prognostic and predictive value in breast and prostate cancer (see, Ignatiadis, M., et al., J Clin Oncol 2007; 25:5194-202; Pachmann, K., et al., J Clin Oncol 2008 (ASCO Annual Meeting abstr 11001); Rack, B. K., et al., J Clin Oncol 2008 (ASCO Annual Meeting abstr 503); Goodman, O. B., et al., J Clin Oncol 2008 (ASCO Annual Meeting abstr 5169); Pittard, G., et al., J Clin Oncol 2008 (ASCO Annual Meeting abstr 5072); Fizazi, K., et al., Ann Oncol 2007; 183:518-21; and Shaffer, D. R., et al., Clin Cancer Res 2007; 13:2023-9). However, these preliminary efforts have been hampered by two significant limitations: (1) CTC isolation and (2) CTC detection. Collecting CTCs has involved a laborious process that employs multiple antibody binding and magnetic bead sorting steps, requiring expensive reagents and equipment, and ultimately yielding a relatively small population of CTCs, which may vary from sample to sample depending on the expression pattern of cell surface markers used in this method. Currently, CTCs are isolated from blood by methods which rely on immuno-magnetic binding of cell surface epithelial cell adhesion molecules (EpCAMs), an expensive, labor-intense approach that is limited to EpCAMexpressing tumors (see, Cristofanilli, M., et al., N Engl J Med 2004; 351:781-91; and Nagrath. S., et al., Nature 2007; 450:1235-9). An alternative platform using a novel parylene-C pore microfilter which traps CTCs quickly and efficiently based on their size differential from other blood cells (See, Zheng, S., et al., J Chromatogr A 2007; 1162:154-61). However, like the EpCAMbased approach, the pore microfilter still relied on fixation, staining, and visual enumeration of captured cells, a laborious and subjective process prone to reader/operator variability. Nevertheless, regardless of the isolation method, it is difficult to derive accurate diagnostic, prognostic or predictive data from absolute numbers of CTCs because of the relative paucity of these cells in peripheral blood.
Therefore, there is a need to develop simple yet highly sensitive and specific cancer detection systems and methods to overcome the above and other problems. The detection systems and methods can be used as a diagnostic, prognostic or predictive assay in patients.